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“Signet ring cell” (SRC) is a phenotypic designation for a cell with a large clear cytoplasmic vacuole displacing the nucleus to the periphery. Our study focuses on the cytopathologic significance of SRCs in the context of diagnostic range, ancillary studies, and clinical prognosis.A retrospective review revealed 83 cases of SRCs diagnosed in a 16-year period (1989-2004). Clinical data and ancillary studies were reviewed.The most common specimen types consisted of abdominal and pleural SCFs (45, 54%). Of the 83 cases, 13 (16%) were benign, 65 (78%) malignant, and 5 (6%) indeterminate. Benign lesions mostly comprised of reactive mesothelial cells (9 cases, 69%). Of the malignant lesions, 47 (72%) were metastases, 14 (22%) were primary cancers and 4 (6%) were local cancer recurrences. Adenocarcinoma was the most prevalent malignant diagnosis (53, 82%). All FNAs with SRCs had a malignant diagnosis. Cytopathologic diagnoses impacted clinical prognosis and survival times.The most common site for occurrence of SRCs is abdominal fluid and their presence usually indicates malignancy (78%). Most cancers with SRCs are metastatic in origin (72%) with a significant proportion from unknown primaries (51%). Cytologic diagnoses of SRCs for cancer have 97% sensitivity and 100% specificity.